Widening the Prostacyclin Paradigm: Tissue Fibroblasts Are a Critical Site of Production and Antithrombotic Protection.

Background: Prostacyclin is a fundamental signaling pathway traditionally associated with the cardiovascular system and protection against thrombosis but which also has regulatory functions in fibrosis, proliferation, and immunity. Prevailing dogma states that prostacyclin is principally derived from vascular endothelium, although it is known that other cells can also synthesize it. However, the role of nonendothelial sources in prostacyclin production has not been systematically evaluated resulting in an underappreciation of their importance relative to better characterized endothelial sources.

Renal Function Underpins the Cyclooxygenase-2: Asymmetric Dimethylarginine Axis in Mouse and Man.

Introduction: Through the production of prostacyclin, cyclooxygenase (COX)-2 protects the cardiorenal system. Asymmetric dimethylarginine (ADMA), is a biomarker of cardiovascular and renal disease. Here we determined the relationship between COX-2/prostacyclin, ADMA, and renal function in mouse and human models.

Clotting Dysfunction in Sepsis: A Role for ROS and Potential for Therapeutic Intervention.

Sepsis is regarded as one of the main causes of death among the critically ill. Pathogen infection results in a host-mediated pro-inflammatory response to fight infection; as part of this response, significant endogenous reactive oxygen (ROS) and nitrogen species (RNS) production occurs, instigated by a variety of sources, including activated inflammatory cells, such as neutrophils, platelets, and cells from the vascular endothelium. Inflammation can become an inappropriate self-sustaining and expansive process, resulting in sepsis.

Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis.

Zinc (Zn) is an essential micronutrient and the second most abundant trace metal in the human body. The important role that Zn plays in hemostasis is exemplified by platelet-related bleeding phenotypes coinciding with dietary Zn deficiency. These phenotypes are rectified upon Zn supplementation.